Life Sciences and Medical

Coherent offers the industry’s broadest selection of lasers and custom total beam sub-systems for life sciences, both in clinical and analytical applications. No matter whether you’re an end user or an OEM, whether your application is flow cytometry, cell sorting, microscopy, multiphoton microscopy, DNA sequencing, or retinal scanning, Coherent has the laser that perfectly matches your needs and your budget.

Coherent was one of the pioneers in the development of laser medicine, and it’s still a very important field for Coherent-deployed lasers today. Because of the technical breadth of the product line, Coherent lasers are used by leading medical system manufacturers for applications as diverse as ophthalmology, dermatology, hair and tattoo removal, surgical, and dental procedures.

DNA sequencing involves the use of automated and miniaturized biochemical techniques to determine the fundamental base sequence (ACGT) of strands of DNA, chromosomes and even the entire genome. DNA sequencing is characterized by its technological diversity, with several completely different high-throughput approaches, each promoted by their suppliers for their superiority in terms of accuracy (i.e., fewer read errors), maximum read length, and cost-effectiveness. These methods feature incredible parallelism that has enabled the cost of genome sequencing to fall by several orders of agnitude in less than 25 years. At present, the most popular of these techniques all rely on laser illumination of fluorescently tagged bases.

The diversity of methodology is reflected in the diversity of laser parameters needed for the different approaches. Some utilize tight focus and use just a few tens of milliwatts, whereas those that rely on wide-field excitation may use lasers at the 1 watt level and beyond. In order to track the four different bases, up to four different visible laser wavelengths are used depending on the fluorophore properties.

In terms of its usage and applications, DNA sequencing is widely used in research but is still in its infancy as a clinical tool. Oncology is a key application area with diagnosis, tumor gene profiling and customized therapies. Sequencing services are also offered as discretionary paid services to consumers fueling market growth. Ultimately, it is expected to play critical roles in the fast growing world of personalized medicine and emerging gene therapies.

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The use of arrays (well plates) revolutionized modern drug discovery and particularly screening, providing unique advantages including automation, miniaturization, and high speed. Array plates have gotten denser over the year and today can total as many as 1,536 separate wells, so imaging speed is of paramount importance in order to view all these wells at high resolution on a practical timescale. High performance array readers are used to image these arrays that are also used in academic research. The combination of laser-based confocal imaging and fluorescent markers in these readers now enables individual cells and even sub-cellular components to be mapped with three dimensional (depth) resolution.

Compact and cost-effective visible lasers with plug-and-play functionality have enabled the development of these next generation array readers, where up to five different excitation wavelengths are used of multi-parameter screening. These wavelengths range from violet/UV 405 nm to red (630 nm). In this way, the same reader might automatically map a genetically expressed fluorescent protein, a nuclear label like DAPI, a membrane stain, and a mitochondrial marker, all in the same fast measurement cycle.

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Raman scattering is a valuable spectroscopic technique that can be applied to solid, liquid or gas samples.

The Raman effect occurs when a sample is irradiated with UV, visible or IR light and a small fraction of the incident radiation is scattered and shifted at frequencies that correspond to vibrational transitions specific of the sample.

The Raman signal is much weaker than the incident and scattered light, so it may be difficult to detect it, unless appropriate measures to enhance the signal/background noise ratio are taken. For example, when a laser source is tuned to match an electronic transition of the sample, the resonant effect increases the Raman scattering by several orders of magnitude. This so-called resonance Raman spectroscopy is often used for applications such as qualitative analysis and molecular structure determination of samples which exhibit electronic transitions in the visible region of the spectrum. For non-resonant Raman spectroscopy, the most commonly used sources are visible or IR laser sources in the range 500 nm to 1,000 nm; shorter wavelength are more likely to excite fluorescence that can easily hide the Raman scattered light, unless the fluorescence is carefully filtered out. For this reason, near-IR light is often used.

Laser sources for continuous wave (CW) Raman spectroscopy include laser diodes, diode-pumped lasers, optically pumped semiconductor lasers (OPSL), and ion lasers. For excitation at fixed wavelengths with CW solid-state lasers, Coherent offers the Sapphire SF single-frequency OPSL series with wavelengths at 488 nm and 532 nm. The Innova 300C and 70C series of small-frame argon or krypton ion lasers are also well suited for Raman experiments in the visible region of the spectrum. Innova 70C Spectrum is a mixed gas lasers that can generate a number of laser lines from the UV to the near IR.

Ultraviolet (UV) resonance Raman spectroscopy is a useful tool for the investigation of molecular structure, kinetics, and excited-state surfaces and dynamics. In particular, it finds numerous applications in systems of biological interest. The Innova series of frequency-doubled argon ion lasers - Innova FRED - is perfect match for resonance Raman spectroscopy because it produces several wavelengths in the range 229 nm to 257 nm. The very short wavelengths of these CW lasers minimize sample damage, compared with nanosecond pulses lasers, and minimize excitation of competing fluorescent signal.

A dynamic field of Raman studies is coherent anti-Stokes Raman scattering, or CARS. This technique uses two synchronized picosecond or femtosecond sources to stimulate a strong signal response at the so-called Anti-Stokes frequency. This happens only when the wavelengths of the two lasers are separated by a wavenumber matching the Raman transition of the sample. This technique is particularly suitable to detect lipids (fats) in microscopic cellular specimens. Ti:Sapphire (Ti:S) lasers and OPOs are well suited for CARS experiments: broad tunability and flexible pulse duration match the application requirements perfectly. Mira-900, Chameleon and Mira-OPO are ideal laser sources for CARS.

Photocoagulation is the prescribed first-choice intervention method for wet-form macular degeneration and diabetic retinopathy, conditions which are estimated to affect up to 250,000 people annually in the U.S. alone. Moreover, this age correlated condition will become even more prevalent with the aging of the baby boom generation.

The Genesis 532 M and 577 M laser family is perfectly suited for photocoagulation treatment of wet-form macular degeneration and diabetic retinopathy. It provides up to 8000 mW at 532 nm and for the unique yellow wavelength of 577 nm up to 5W. This new yellow wavelength is exclusively available from our proprietary OPSL technology and exactly matched to the main absorption peak of oxygenated hemoglobin. It provides a higher degree of tissue selectivity than any previous laser wavelength. This delivers superior results with reduced patient discomfort.

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A rapidly growing field combining molecular biology with optical stimulation of light-sensitive proteins to target specific regions of a single cell or a group of cells within the brain.

Optogenetics is about turning on and switching off neurons by optical stimulation using light sensitive proteins. The first light-activated proteins isolated from a species of green algae in 2002 were Channelrodopsin-1 and -2. When activated with appropriate light, these proteins open the channel for a flux of positive ions into the cell to activate neurons and to trigger voltage signal propagation (the so-called action potential). Halorodopsin does the inverse (with negative ions) to deactivate neurons.

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Multiphoton Excitation (MPE) microscopy was first reported in 1990 (Denk, Strickler and Webb). Since then, it has grown to become an ubiquitous imaging technique when in-vivo, optical sectioning is key. In multiphoton microscopy, a fluorescent molecule – attached to the specimen or naturally present – is excited by two or three photon of infrared light. This is in contrast with confocal microscopy where the same type of molecules are excited by a single photon of blue-green or UV light. Multiphoton excitation offers several fundamental advantages over confocal microscopy: the IR light penetrates more deeply in the tissue because of lower absorption and scattering; the longer wavelength is less damaging and allows in vivo imaging also in human subjects; finally, the non-linear process excite fluorescence only on the focal plane and a the confocal aperture required with single-photon excitation is no more necessary. The sectional image of a living mouse brain, imaged to a depth of 800 micron with Coherent Chameleon Ultra II laser is an impressive paradigm of the capability MPE.

In parallel to MPE, several other non-linear techniques have become increasingly popular. These include Second Harmonic Generation (SHG) microscopy and Coherent Anti-Stokes Raman Spectroscopic (CARS) microscopy. This suite of non-linear techniques require the use of Ultrafast lasers, generating pulses of 100-200 fs and tunable over the near IR region of the spectrum. These lasers are inherently more complex than the blue-green lasers used for confocal microscopy and other bioinstrumentation applications.

Coherent recognizes that microscopists, neurologists and biologists should not have to become laser experts to do their work. For this reason we designed and manufacture and expansive line of lasers designed specifically for non-linear imaging. This way, MPE users can focus on their sample, not on the laser equipment.

Myopia, astigmatism, and hyperopia can all be treated effectively with non-thermally damaging and precisely controlled lasers.

Laser vision correction has revolutionized eye surgery. Myopia, astigmatism, and hyperopia can all be treated effectively with the non-thermally damaging and precisely controllable ArF excimer laser beam. This technique has already helped millions of people since the early 1990s to enjoy life without glasses or contact lenses. Coherent is the leading supplier of light sources for this rapidly-expanding industry.

By being the first to engineer extremely reliable, high-repetition-rate excimer lasers specifically for this application, we have become the supplier of choice for many industry leaders in vision correction. Being successful in this industry depends not only on laser performance, but also on the quality of the system. Because laser vision correction is not a medical necessity, it is considered cosmetic surgery and as such it is closely supervised by the FDA and other regulatory agencies around the world. These regulatory bodies require the highest standards in product quality and safety.

All Coherent systems meet or exceed these standards and we continue to maintain and improve our comprehensive ISO 9001:2000 quality-management system.

Today, Coherent is the leading supplier of excimer lasers for refractive error correction systems. At least 35% of all refractive surgeries (more than 1 million procedures annually) are performed with our lasers. We continue to be the industry leader as we supply the next step in refractive surgery technology: customized vision correction.

The diagrams show the principle of cornea reshaping for myopic and hyperopic vision correction and laser application. The accuracy of the ArF excimer laser ablation is essential for the predictability and safety of laser vision correction. Only this laser source enables the precise reshaping in the necessary sub µm range.

Images courtesy of VSDAR, Munich

Summary
Correction of refractive errors (shortsightedness and farsightedness as well as astigmatism) with an excimer laser is a safe and effective procedure which can restore the natural vision of the patients.

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Flow Cytometry is a diagnostic tool most commonly used to analyze the immune or genetic characteristics of cells.

Cells from a sample are mixed with a dye which preferentially binds (called tagging) to a cellular component. The sample is then illuminated with laser light, causing the dyes to fluoresce. The fluorescence emission is spectrally filtered to separate the signals. Quantitative analysis of the respective signal strengths yields a distribution of the blood components within the sample. The current generation of dyes is excited by 488 nm laser light.However, recent work suggests that a new generation of dyes which fluoresce when pumped by 532 nm light can provide even more information.

Our Sapphire laser portfolio began with the offering of the world´s first solid-state 488 nm laser. This diode-pumped laser family offers significant performance, size and efficiency advantage over traditional air-cooled gas lasers. For recent progress with 532 nm excitation, we offer the Compass family of DPSS lasers. Our CUBE and Genesis lasers also offer products with wavelength ranges ideal for fluorescence emission.

Unlike the mature technology of conventional MRI, enhanced MRI technology and applications are still evolving and therefore require a flexible and well designed laser to meet the demanding needs of both OEM customers and research laboratories. The latest generation of Coherent semiconductor laser bars and systems, with increasingly higher power-spectral density, enables exciting new possibilities and emerging novel applications for laser induced hyperpolarized noble gas imaging.

By offering the widest variety of wavelength options and allowing the end user to easily exchange different wavelengths in a few minutes, Coherent diode lasers offer the flexibility to pump rubidium, potassium, and other atomic vapors used in the spin exchange process.

In the field of dermatology we serve a number of applications. Our CO2 lasers and semiconductor diode lasers are widely adopted in the areas of tattoo removal and hair removal, and our waveguide technology with CO2 lasers is the leading technology in the rapidly growing fractional skin resurfacing application. More recently, system builders have begun to use our visible Optically Pumped Semiconductor Lasers (OPSLs) in the treatment of pigmentation, blood vessels or wrinkles because of its better absorption of yellow wavelengths in melanin compared to legacy green laser solutions.

Breakthrough treatments for psoriasis and vitiligoPsoriasis are being discovered. These are chronic, recurring skin conditions with no known cure. It produces red, scaly skin plaques that causes discomfort and disfigurement. It is the second most common skin disorder in the United States, Europe and Countries with little sun exposure. The cost for conventional treatment approaches such as phototherapy (broadband UVB, PUVA), topical and systemic medication sum up to high expenses and promise only temporary relief.

Several large multicenter clinical trials have demonstrated the success of a new 308 nm laser therapy to treat the symptoms of Psoriasis. A beam generated by an excimer laser is aimed precisely at the involved skin without exposing normal skin, reducing the risks of conventional phototherapy such as photoaging.

In contrast to traditional treatments first results are visible after only a few treatments and they promise to be long-lasting, symptoms disappearing for 6 or even more than 12 months. Most patients heal in between 6 and 12 sessions, vastly reducing the number of required treatments and increasing compliance.

Recently introduced the new laser treatment is now revolutionizing the psoriasis therapy. Patients with small plaques (up to 35cm²) can be treated within one minute, for patients with larger lesions and dark skin types the treatment may take 5 to 15 minutes.

For the first time a quick and effective treatment for psoriasis can be offered, ending patient and doctor frustration. The intense, narrow band 308 nm radiation of the XeCl excimer laser has shown to be very beneficial for the treatment of vitiligo and leukoderma as well.

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Yields a series of high-resolution, high-contrast images that can be reassembled into a three-dimensional picture.

The microscope is confocal because the objective lens is used both to illuminate the sample and to image it. It is a scanning optical microscope because only one point of the sample is illuminated at a time. As the sample is scanned, the image is built up pixel by pixel. True optical sections of a sample are taken because of the short focal plane of the objective lens (as small as .5 microns). Any image data above or below the focal plane is prevented from reaching the detector. Levels of the sample are collected as the focal plane (Z axis) is raised or lowered. These levels are then computer-assembled into a three dimensional structure. Features of a confocal microscope include high-resolution, submicron microscopy, without the expense of an electron microscope, magnification ranging from 100x to 10,000x, and non-destructive examinations of living samples. Confocal Microscopes are used in the following applications:

Confocal Microscopes are used in the following applications:

Tissue research in cytological and neurological applications

Fluorescence observations in biology and medicine

Semiconductor UV metrology

High resolution defect analysis and topography profiles in semiconductors

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Efficient and reliable illumination sources for bio-detection and biomedical applications.

Coherent’s structured light lasers, when used in conjunction with our Flat Top Projector refractive beam shaper, can illuminate an area with uniform intensity for use in applications where scanning or inspection of biological molecules over a given area is necessary. New developments in the photonics field and the increase in demand for biological agent identification systems have created a new need for efficient and reliable illumination sources for such applications.

Risk factors: Except for the historical information contained here, many of the matters discussed in this Web site are forward-looking statements, based on expectations at the time they were made, that involve risks and uncertainties that could cause our results to differ materially from those expressed or implied by such statements. These risks are detailed in the “Factors That May Affect Future Results” section of our latest 10-K or 10-Q filing. Coherent assumes no obligation to update these forward-looking statements.